Growth and gene expression profile analyses of endometrial cancer cells expressing exogenous PTEN

The PTEN tumor suppressor gene encodes a multifunctional phosphatase that p lays an important role in inhibiting the phosphatidylinositol-3-kinase path way and downstream functions that include activation of Akt/protein kinase B, cell survival, and cell proliferation. Enforced expression of PTEN in va rious cancer cell lines decreases cell proliferation through arrest of the cell cycle, accompanied in some cases by induction of apoptosis. We used cD NA microarrays containing 4009 cDNAs to examine changes in gene-expression profiles when exogenous PTEN was induced in PTEN-defective cells. The micro arrays and subsequent semiquantitative reverse transcription-PCR analysis r evealed transcriptional stimulation of 99 genes and repression of 72 genes. Some of the differentially expressed genes already had been implicated in cell proliferation, differentiation, apoptosis, or cell cycle control, e.g. , overexpression of PTEN-induced transactivation of cyclin-dependent inhibi tor 1B (p27Kip1) and 2B (p151NK4B), members of the TNF receptor family, tum or necrosis factor-associated genes, and members of the Notch-signaling and Mad families. To our knowledge this Is the first report of transactivation of those genes by PTEN. The genes differentially expressed in our experime nts also included many whose correlation with cancer development had not be en recognized before. Our data should contribute to a greater understanding of the broad spectrum of ways in which PTEN affects intracellular signalin g pathways. Analysis of expression profiles with microarrays appears to be a powerful approach for identifying anticancer genes and/or disease-specifi c targets for cancer therapy.